People suffering from a large number of diseases experience chronic psychological stress that disrupts normal metabolic, hormonal, and steroidal processes. Abnormal metabolic, hormonal, and steroidal profiles are characteristically different from those of both non-stressed individuals and otherwise healthy individuals exposed to mental and physical stresses—even if those stresses are severe. In healthy individuals, stresses are mediated via a complex and interconnected human steroidal hormone cascade, and the natural response to these stresses is manifested as temporarily increased or decreased levels of certain hormones throughout the cascade. Temporary increases and decreases are a normal and healthy response that restores balance to the entire cascade. In healthy individuals, temporary increases and decreases in certain hormonal levels, often referred to as “up regulation” and “down regulation” successfully restores balance to the hormonal cascade and a normal and natural restoration of the cascade is a hallmark of a healthy response to both mental and physical stress.
Even when stress is extreme, short term stresses, typically measured in terms of hours to days, in healthy individuals illicit a reliable and appropriate hormonal cascade response to counteract the stresses. This normal and healthy response is measurably and fundamentally different than the response exhibited by patients suffering from chronic mental stress. For example, elite soldiers subjected to extreme survival training exercises involving starvation and sleep deprivation during survival training regimens exhibit temporary and increases or up regulation of anti-inflammatory hormones in the upper level of the hormonal cascade . . . down regulation of estradiol in addition to testosterone and temporary suppression of the immune system is observed although also reversed in the short to intermediate term.
In contrast, some individuals who suffer from chronic psychological physical stress exhibit massive and sustained disruptions in the entirety of the hormonal cascade that is unique and characterized by widespread up regulation of hormones at the “top” of the cascade—hormones that are well recognized as related to stress and anxiety. Hormones at the “bottom” of the cascade, known to be critical to cellular immunity, and are required for protection from infection, inflammation, allergies, protection from cardiovascular disease, healthy barrier function, and cell repair, are dramatically reduced or down-regulated across the entire cascade.
Moreover, the specific hormonal imbalances between the anxiety hormones at the upper portion of the cascade and the immune-protective hormones at the bottom of the cascade is characteristic chronic stress disorders and causes an entire range of comorbidities, including tendency to physical accidents, depression, hyperlipidemia, atherosclerosis, by failure of the immune system, suicide, and an overall significant and measurable reduction in life expectancy. These comorbidities are not seen in healthy individuals whose hormone cascade exhibits a natural and normal response to stress.
As an example, the normal up-regulation of cortisol in response to severe short-term stress performs a valuable function by reducing inflammation. However, in abnormal chronic stress conditions, cortisol is down regulated in response to chronic emotional or psychological stress. The healthy up-regulation of cortisol beneficially stimulates the immune system whereas the abnormal down regulation leads to dangerous comorbidities including hypertension, increases in cholesterol and triglycerides, increased susceptibility to viruses and other pathogens, joint pain, gastrointestinal disorders, increased cancer risk, increased food and other allergies, increased G.I. disease, and an increased risk of autoimmune disease.
Significant hormone imbalances are seen most typically in conditions that, contrary to short-term physical and mental stresses, involve permanent and continuous exposure to stress that has a primary psychological component, even though physical stresses may also be present. Although the causes, progression, the physical symptoms of these diseases can vary greatly, the common component is continuous and significant psychological stress that unbalances the hormonal cascade resulting in increase in the entire range of anti-inflammatory hormones and a decrease in the immune protective components. Thus, although chronic stress disease conditions such as severe mental disease, post-traumatic stress disorder, schizophrenia, bipolar disease, and other chronic conditions have a wide range of underlying causes and impact dramatically different patient populations, each is accompanied by an identifiable stress response in the human steroidal hormone cascade. Also, in these afflicted populations, the characteristic stress responses have no tendency to normalize over time and display a broad-based shift in hormonal values across the cascade that is abnormal and causes a broad range of other pathologies and comorbidities.
Severe mental diseases (including Post Traumatic Stress Disorder (PTSD), schizophrenia, bipolar disorder) are accompanied by co-morbidities including systemic pain, hyperarousal, depression, insomnia, and cognitive and behavioral abnormalities. Patients suffering from severe mental diseases in chronic stress exhibit an abnormal lipid profile that leads to increased risk of stroke and heart attack, increased risk of immune disorders, metabolic syndrome, and systemic inflammation, inflammatory bowel diseases, atherosclerosis, viral and bacterial infections.
Although chronic, untreated stress disorders have a variety of treatment options, including drugs and psychological counseling, none of the existing treatments address the characteristic and chronic imbalance in the steroidal hormone cascade. While individual elements of the cascade have been addressed by prior treatments, no known attempts have yielded a unified, yet multi-faceted approach to re-balancing the hormonal cascade, especially by reversing the global up regulation of the production of hormones at the top of the cascade and global down-regulation of hormones at the bottom of the cascade
Therefore, a need exists for new formulations and medicinal compositions and disease-specific methods of treatment that promote re-balancing of the human steroidal hormonal cascade to counteract the abnormal up-regulation of certain selected hormones and the abnormal down-regulation of other hormones. Counteracting this imbalance will reduce the adverse effects of the chronic distortion of the hormonal cascade and by restoring healthy hormonal balance, ameliorate the symptoms caused by the imbalance, including reduction of the direct symptoms of stress-related disorders, both psychological and physical, and including the related comorbidities.